Infants exposed to methadone in utero were compared to infants of drug-free women at 4, 8, and 12 months on two aspects of their behavior: motor coordination and attention. The purpose of this paper is to discuss how differences between the methadone and comparison infants were affected by other family and medical risk factors. No matter what the level of other risk factors, methadone infants showed poorer motor coordination at 4 months and poorer attention at 12 months as a group than comparison infants. Family risk factors, however, did modulate the strength and direction of differences between methadone and comparison infants. After 4 months, methadone infants continued to show poorer motor coordination than comparison infants only in families with poorer resources (such as low SES, maternal psychopathology and low intelligence, absence of father). Poorer early medical resources (pre- and perinatal complications) heightened the differences between methadone and comparison infants at early ages, but by the end of the first year no longer played a role in modulating the drug effect. The authors tentatively conclude that methadone exposure in utero has very limited teratological effects per se on the long-term development of infants, and that the pathology seen in some individual children is probably due to an interaction with other factors.